Characterization of the Vitamin D System in Normal and Hypertrophied Heart

正常和肥厚心脏中维生素 D 系统的特征

• 批准号: 7354079
• 负责人: DENIS J GLENN
• 金额: $ 5.59万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7354079
• 关键词: Cardiac; Cardiac Myocytes; Cardiovascular Physiology; Cells; Fibroblasts; Heart; Heart Hypertrophy; Hypertrophy; Knockout Mice; Mixed Function Oxygenases; Modeling; Mus; Muscle Cells; Neonatal; Receptor Gene; Stimulus; System; Tissues; Vitamin D; Vitamin D3 Receptor; Vitamins; autocrine; in vivo; paracrine; response

DESCRIPTION (provided by applicant): Vitamin D directly inhibits key phenotypic features of cardiac hypertrophy raising the possibility that it may function in an autocrine or paracrine fashion to suppress hypertrophy. However, for this hypothesis to be valid requires that cardiac cells possess the ability to regulate and respond to the active form of vitamin D. The components of the vitamin D system, specifically the VDR, 1 alpha-hydroxylase and 24-hydroxylase, will be examined and the response to hypertrophic stimuli characterized. The importance of vitamin D in cardiovascular function is supported by studies of the vitamin D receptor (VDR) knockout mouse, which develops cardiac hypertrophy. However, the underlying mechanisms involved are difficult to interpret given the pleiotropic effect of vitamin D. To determine the direct effects of endogenous vitamin D on the myocyte will require a tissue specific model, and so a cardiac-selective deletion of the murine VDR gene will be created and the response to a hypertrophic stimulus will be assessed in vivo.

描述（由申请方提供）：维生素D直接抑制心脏肥大的关键表型特征，提高了其可能以自分泌或旁分泌方式发挥作用以抑制肥大的可能性。然而，要使这一假设有效，需要心脏细胞具有调节和响应维生素D活性形式的能力。将检查维生素D系统的组分，特别是VDR、1 α-羟化酶和24-羟化酶，并表征对肥大刺激的反应。维生素D在心血管功能中的重要性得到了维生素D受体（VDR）敲除小鼠研究的支持，该小鼠会发生心脏肥大。然而，由于维生素D的多效性作用，所涉及的潜在机制难以解释。为了确定内源性维生素D对肌细胞的直接影响，需要组织特异性模型，因此将创建鼠VDR基因的心脏选择性缺失，并在体内评估对肥大刺激的反应。